Hemochromatosis is a genetic disorder characterized by an excess of iron accumulation in the body, causing in the course of the time injuries in different organs and tissues, particularly in liver, myocardium, pancreas, kidney, spleen, gonads and skin. Idiopatic Hemochromatosis is the most wide-spread hereditary disease in the Western population (incidence 1:300) and it is characterized by a recessive inheritance. This kind of Hemochromatosis was at first associated to HFE gene mutations (Hereditary Hemochromatosis described in Feder et al., Nat. Genet. 1996, 13:399-408). More recent studies have at first supposed and then proved that mainly in South-Western population, other genes in addition to HFE could have a role in Idiopatic Hemochromatosis (Piperno et al, Gastroenterology 1998, 114: 996-1002 and Borot et al, Immunogenetics 1997, 45: 320-324).
Some mutations in the ferroportin gene, recently named SLC40A1 and previously known as SLC11A3 or IREG-1 or MTP-1, have indeed already been identified both by the authors of the present invention and by others as described for instance in Montosi et al., J. Clin. Invest, 2001, 108:619 and In WO 02/033119; Devalia V. et al., Blood, 2002, 100:695; Cazzola et al., British Journal of Hematology 2002, 119:539; Wallace et al., Blood, 2002, 100:692; Njajou Nat. Genet. 2001, 28:213.
The identification of most of the genetic alterations responsible for Hereditary Hemochromatosis or diseases linked to impaired iron homeostasis is of great importance both in diagnostics and therapeutics. In fact, till today the diagnosis of Hemochromatosis is delayed and it is based on clinical symptomatology developed as a consequence of tissue injuries which are frequently irreversible. Moreover the diagnosis of such disease is made difficult by the fact that its symptoms are often similar to those of other diseases characterized by impaired iron homeostasis.
The development of methods of genetic screening for the early diagnosis in a presymptomatic stage, of the Hereditary Hemochromatosis would allow to operate in time by phlebotomy to prevent in this way damages to organs and tissues.
Moreover the identification of genetic alterations linked to Hereditary Hemochromatosis and the comprehension of their role in the development of the pathology, are most relevant for the optimization of new and improved therapeutic strategies.